Molecular heterogeneity of β‐thalassaemia in the Japanese: identification of two novel mutations

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Abstract
Five unrelated Japanese β‐thalassaemia genes, from one homozygote and four heterozygotes, have been systematically characterized using DNA polymorphism analysis, polymerase chain reaction, dot‐blot hybridization and direct sequencing of amplified genomic DNA. Four different molecular defects were observed on three different β‐globin gene frameworks. One of these, the A→G mutation in the TATA box, a previously described mutation, was detected by dot‐blot hybridization in one homozygote and one heterozygote with the β‐globin gene of framework 2. The second mutation is a C→T substitution at position 654 of IVS‐2, the mutation commonly found in Chinese, which was associated with the framework 1 gene. Another two mutations, both associated with framework 3 genes, are novel ones; an amber mutation in codon 90 (GAG to TAG) and a frameshift (+G) insertion in codon 54, both of which cause a β0‐thalassaemia phenotype by premature termination of the β‐globin chain synthesis.